The mechanisms underlying the neuroglial response to injury (fibrous gliosis) and the similarities and differences of glial fibrillary acidic (GFA) protein compared to other filamentous proteins in the brain will be investigated. A number of animal models will be used for the experimental production of fibrous gliosis. The proposed studies include: 1. Comparison of GFA in normal and gliosed brain; 2. Sequencing of GFA (in collaboration with Dr. Moo-Penn); 3. Physicochemical properties of GFA. The nature of covalent and non-covalent interactions leading to the indefinite association of subunits to form filaments in vivo both in normal and gliosed brain. Assembly of filaments in vitro; 4. Quantitation of GFA in buffer and urea extracts by microcomplement fixation; 5. Turnover and degradation of GFA in normal and gliosed brain; 6. Limited proteolysis by GFA peptidase(s) and its physiological significance (posttranslational cleavage of GFA in the assembly of glial filaments or initial step in degradation); 7. Biochemical and immunological comparison of glial and axonal filaments; 8. Isolation of neurofilament protein, water-soluble fraction; 9. GFA expression in the C-6 cell line; and 10. On the glial cell surface in vitro. It is hoped that this research will contribute to the understanding of fibrous gliosis and eventually lead to the development of procedures for the control of this process. Glial scarring may be related to the lack of functional repair in the mammalian CNS (axonal regeneration in spinal cord injury; remyelination in multiple sclerosis), epileptogenesis, deficient myelination in the developing brain.